Delving into the Latest Updates on CDK6 inhibitors(ViroStatics) with Synapse

Overview

Basic Info

Drug Type

Chemical drugs

Synonyms-

Target

CDK6

Action

inhibitors

Mechanism

CDK6 inhibitors(Cyclin-dependent kinase 6 inhibitors)

Therapeutic Areas

Respiratory Diseases

Active Indication

Respiratory Distress Syndrome, Acute

Inactive Indication-

Originator Organization

Virostatics Srl

Active Organization

Virostatics Srl

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Targeting cyclin-dependent kinase 6 (CDK6) in cancer treatment is a promising strategy due to the central role of this enzyme in regulating cell proliferation. As research continues, more selective CDK6 inhibitors may emerge, potentially offering even greater specificity and fewer side effects. Xanthatin as a bioactive sesquiterpene lactone extracted from Xanthium strumarium L., has recently been revealed to have potential anticancer activities. However, the anticancer mechanisms triggered by xanthatin in prostate cancer (PCa) cells are not fully investigated. MTT and colony formation assays were performed to detect the cytotoxicity of xanthatin in DU145 cells. Also, HUVEC was used as a noncancerous cell line model. Oxidative stress marker, qRT-PCR and ELISA assays were performed to analyze the ROS stress and apoptosis as well as th downregulation of CDK6. Fluorescence quenching, circular dichroism, UV-visible, molecular docking, and molecular dynamics simulation studies were also done to explore the interaction of xanthatin with CDK6. The results showed that xanthatin significantly and selectively repressed the viability of PCa cells in a concentration-and time-dependent manner, while the IC50 values of xanthatin for PCa cells and HUVEC were 9.95 μM and 48.85 μM, respectively after 48 h. Xanthatin markedly increased oxidative stress marker production mediated by downregulation of GSH and SOD. Furthermore, xanthatin treatment resulted in overexpression of caspase-3 and downregulation of CDK6. Furthermore, it was shown that xanthatin strongly binds with CDK6 with a logK_b value of 5.53 ± 0.32 in a 1:1 M ratio with the aid of hydrophobic forces derived from ILE19, ALA41, LEU152, VAL101, VAL27, PHE98, and HIS100 residues. Moreover, xanthatin resulted in an increase in the protein dynamics, fluctuation and structural changes which resulted in inhibition of enzyme activity. The results of this study may underscore the potential of xanthatin in the development of anticancer therapies, specifically as a CDK6 inhibitor.

01 Mar 2025·World Journal of Pediatrics

From low remission to hope: the efficacy of targeted therapies in NUP98-R positive pediatric acute myeloid leukemia

Article

Author: Xiong, Run-Ji ; Tang, Hong-Xia ; Pan, Hui-Yi ; Yin, Tian-Tian ; Jin, Run-Ming

Abstract:

Background:

Treating pediatric acute myeloid leukemia (AML) with NUP98 rearrangement (NUP98-R) is challenging. Standard chemotherapy results in low remission rates. This study aimed to evaluate different induction regimens and explore alternative therapies to improve outcomes.

Methods:

This retrospective study included 111 pediatric patients with AML treated at our institution from March 2012 to March 2023. Patients were classified into two groups: NUP98-R-positive (n = 10) and NUP98-R-negative (n = 101). We compared their clinical characteristics, treatment responses, and prognoses. Additionally, we presented three cases of NUP98-R-positive patients to elaborate on the role of targeted therapies during induction in treatment outcomes and prognosis.

Results:

Patients with NUP98-R fusion genes had a complete remission (CR) rate of 20% after the first induction, which was significantly lower than the 64.3% reported in those without NUP98-R fusion genes (P < 0.05). The 3-year event-free survival (EFS) rate was also lower, with only 30% for NUP98-R patients and 55.3% for non-NUP98-R patients (P < 0.05). The prognosis of NUP98-R patients improved with targeted therapies during induction. For example, Patient 1 achieved CR with FLT3 and BCL-2 inhibitors plus conventional chemotherapy. Patient 2, who was treated with a CDK6 inhibitor, a BCL-2 inhibitor, azacitidine, and an FLT3 inhibitor, also achieved CR and underwent successful stem cell transplantation. Conversely, Patient 3, who received only standard chemotherapy, did not achieve remission and died from a severe infection.

Conclusions:

This study demonstrated that using targeted drugs for the induction in NUP98-R pediatric AML improved treatment outcomes. BCL-2, FLT3, and CDK6 inhibitors available at our institution are promising options for this phase of treatment.

Graphical abstract:

18 Feb 2025·International Journal of Biological Sciences

IGF2BP3 promotes the proliferation and cisplatin resistance of bladder cancer by enhancing the mRNA stability of CDK6 in an m6A dependent manner

Article

Author: Yu, Hao ; Zhou, Zijian ; Lv, Jiancheng ; Wang, Wei ; Lu, Qiang ; Yang, Xiao ; Song, Qiang ; Jiang, Linjing ; Yang, Haiwei ; Zhuang, Juntao

Cisplatin-based chemotherapy is a primary treatment for bladder cancer, yet the development of chemoresistance poses a significant therapeutic challenge. Insulin-like growth factor II mRNA binding protein 3 (IGF2BP3) is an RNA-binding protein and a key m6A reader that regulates various cancers through m6A-dependent mechanisms. However, its role in chemotherapy resistance in bladder cancer remains unclear. Our in vivo and in vitro experiments identified IGF2BP3 as a key regulator of cisplatin resistance in bladder cancer. We demonstrated that IGF2BP3 enhances the stability of CDK6 mRNA in an m6A-dependent manner, leading to increased CDK6 expression. This, in turn, promoted tumor cell proliferation and resistance to cisplatin chemotherapy. Moreover, we showed that the CDK6 inhibitor palbociclib effectively suppresses the pro-growth and chemoresistant effects induced by IGF2BP3 overexpression. These results suggested that the IGF2BP3/m6A/CDK6 axis plays a pivotal role in bladder cancer progression and chemoresistance, and that targeting this pathway with CDK6 inhibitors such as palbociclib may offer a promising therapeutic strategy for overcoming cisplatin resistance in bladder cancer.

100 Deals associated with CDK6 inhibitors(ViroStatics)

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